1. Field of the Invention
This invention is directed to methods and formulations for the treatment or prevention of infections on mammalian tissues such as skin. Specifically, the methods of this invention involve the in situ formation of a polymeric cyanoacrylate film containing mixed antibiotics over mammalian tissue.
2. References
The following patents are cited in this application as superscript numbers:                1 Barley, “Methods for Retarding Blister Formation by Use of Cyanoacrylate Adhesives”, U.S. Pat. No. 5,306,490, issued Apr. 26, 1994.        2 Barley, et al., Methods for Treating Suturable Wounds by Use of Sutures and Cyanoacrylate Adhesives, U.S. Pat. No. 5,254,132, issued Oct. 19, 1993        3 McIntire, et al., Process for the Preparation of Poly (α-Cyanoacrylates), U.S. Pat. No. 3,654,239, issued Apr. 4, 1972        4 Barley, et al., Methods for Treating Non-Suturable Wounds by Use of Cyanoacrylate Adhesives, U.S. Pat. No. 6,342,213, issued Jan. 29, 2002.        5 Barley, et al., Methods for Reducing Skin Irritation From Artificial Devices by Use of Cyanoacrylate Adhesives, U.S. Pat. No. 5,653,789, issued Aug. 5, 1997        6 Tighe, et al., Methods for Inhibiting Skin Ulceration by Use of Cyanoacrylate Adhesives, U.S. Pat. No. 5,403,591, issued Apr. 4, 1995        7 Tighe, et al., for Use of Cyanoacrylates for Providing a Protective Barrier, U.S. Pat. No. 5,580,565, issued Dec. 6, 1996        8 Askill, et al., for Methods for Draping Surgical Incision Sites, U.S. Pat. No. 5,807,563 issued Sep. 15, 1998        9 Greff, et al., for Cyanoacrylate Compositions Comprising an Antimicrobial Agent, U.S. Pat. No. 5,684,042, issued Nov. 3, 1997        
All of the above patents are herein incorporated by reference in their entirety to the same extent as if each individual patent was specifically and individually indicated to be incorporated by reference in its entirety.
3. State of the Art
Many commercial topical antibiotic preparations exist in creams, lotions, petroleum bases, etc. While they are easily applied, they are also easily rubbed off (e.g., ointments applied to the skin frequently rub off onto the patient's clothing within minutes or hours thereby losing their effectiveness). This problem is most commonly addressed by applying protective layers or covers such as dressings over the ointments.
The covers, while simple to use, can absorb the ointment or cause it to displace to another area. The ointment can also prevent the adhesive on the dressing from effectively adhering. In some cases, attempts have been made to incorporate the active ingredients in pre-formed films or in film-forming solutions. Unfortunately, most preformed films have limited diffusion of the active ingredients and show little or no clinical activity.
Greff, et al.9 have demonstrated that certain iodophors can be incorporated into prepolymeric cyanoacrylate compositions to create stable film forming liquids wherein the iodophor effectively provides for antimicrobial activity to the polymer film formed therefrom. However, many antimicrobial agents are incompatible with prepolymeric cyanoacrylate compositions causing either immediate polymerization or preventing polymerization from occurring at all or within a reasonable period of time after application to mammalian tissue. In addition, while insoluble antibiotics appear to cause less rapid effects on the performance of the prepolymeric cyanoacrylate compositions, these materials will most frequently fall out of suspension and resist re-suspension. This is particularly disadvantageous where the mixing potential is restricted by the size of the container, e.g., a single use package.
Heretofore, prepolymeric cyanoacrylate compositions have been disclosed for use in a variety of medical environments such as an alternative or adjunct to sutures2 or as a hemostat3. Other described uses of cyanoacrylate prepolymers include their use on mammalian tissue to form polymeric films which are utilized:
to prevent friction blister formation1,
in treating small non-suturable wounds4,
in inhibiting surface skin irritation arising from friction between the skin surface and artificial devices such as tapes, prosthetic devices, casts, etc.5,
as surgical incise drapes8,
in inhibiting skin ulceration6, and
forming a protective film to inhibit skin degradation due to incontinence.7 
In each case, the combination of conventional antibiotics with these compositions would be useful particularly as a replacement for conventional bandages.